Abstract Summary: Failure to deliver care near the end of life that reflects the needs, values and preferences of patients with advanced cancer remains a key shortcoming of our cancer care delivery system. National organizations including the National Academy of Medicine and American Society of Clinical Oncology have called for increased attention to advance care planning (ACP) to improve patient-centered care near end of life. A critical barrier to progress in the field is a lack of evidence about the most effective and efficient ACP strategy to improve treatment decisions near end of life and ensure patients' wishes are honored. Two different patient-facing ACP interventions are widely used and known to be effective but entail sizeable differences in costs and complexity to deploy: (1) in-person discussions with trained facilitators and (2) web- based advance care planning using interactive videos. These approaches have never been compared directly; it is therefore unclear whether one form of ACP is more potent?and if so, for whom and under what circumstances. Understanding the relative effectiveness of in-person, facilitated versus web-based ACP is important because in-person ACP requires far more resources. This proposal is a single-blind, patient-level randomized trial to address this evidence gap, using mixed methods to compare the effectiveness of in-person, facilitated ACP vs web-based ACP among 400 patients with advanced cancer and their family caregivers. Aim 1 compares the effect of these approaches on patient and family caregiver outcomes (engagement in ACP?primary outcome; ACP discussions with family caregivers and physicians; advance directive (AD) completion; and caregiver symptoms of depression and anxiety). For patients who die during the study period, we will use validated, caregiver-reported measures to compare perceived quality of EOL care, patients' EOL goal attainment, and bereaved caregiver symptoms of depression, anxiety and post-traumatic stress. Aim 2 assesses implementation costs of each intervention and effects on healthcare utilization at end of life. Aim 3 identifies contexts and mechanisms influencing the effectiveness of each approach. This trial will have a high impact because it will provide new and much-needed empirical evidence about two patient-facing ACP approaches that successfully overcome limitations of traditional written advance directives but entail very different investments of time and resources. It is innovative in using mixed methods to evaluate not only the comparative effectiveness of these approaches, but also for whom, how and in what circumstances they are effective. It is feasible because it builds on extensive infrastructure developed by an accomplished research team with experience conducting behavioral intervention trials and qualitative research in ACP and oncology.